A research “dream team”

Dana-Farber, Merck team up to focus on cancer drug development

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BOSTON—In an effort to improve the success rate of investigational cancer drugs entering clinical trials, the Dana-Farber Cancer Institute's Center for Applied Cancer Science (CACS) and Merck and Co., Inc., have forged a collaboration to identify potential drug targets, and develop therapeutic candidates to reach those targets.

"Currently, there is a 95 percent failure rate in cancer drug development," says Dr. Ronald DePinho, of the CACS. "Drugs that pass safety testing in Phase I trials too often fail to show efficacy in later-stage trials, or prove effective in only a small subset of patients. The failure rate in Phase III is 50 percent."

According to the partners, terms of the deal call for New Jersey-based Merck to provide up-front funding and research support to the Boston-based cancer research center as well as milestone and royalty payments on market approval. Exact financial details of the deal are not being released, but a Dana-Farber spokesman said the institute likely will hire additional staff members to support the research.

The CACS consists of a team scientists and core laboratory facilities for identifying genetic alterations in cancer, pinpointing those alterations most crucial to tumor formation and maintenance, validating those targets in a wide range of cell and tissue cultures assays and sophisticated animal models, and, in the case of monoclonal antibodies, developing them into useful therapies.

The CACS retains the right to develop its antibodies independent of the Merck collaboration.

Dana-Farber's Lynda Chin will be the senior investigator in the Dana-Farber-Merck alliance, which plans to use genomic information in identifying therapeutic targets.
The use of genomic information in identifying therapeutic targets and appropriate trial designs requires the integration of genomics with function, mechanism and, importantly, cancer biology, explains Chin.

The companies, DePinho notes, will work together to develop targets, validate targets and follow the process all the way through the clinical trials.

According to DePinho, those failures occur primarily because companies don't do enough due diligence on the targets being enlisted into the drug development process.  "We don't really determine whether the target is a tumor-maintenance gene."
Under the collaboration, the CACS will investigate drug targets using integrative and cross-species genomic analysis and stringent multi-level functional and clinicopathological validation testing.

DePinho also points out the CACS will work together with Merck to shepherd the drug assay development of lead compound discovery and then work together to test these drugs in CACS's highly sophisticated model systems that closely replicate human disease.

The collaboration will also involve members of CACS faculty, under the direction of Drs. James DeCaprio and Kenneth Anderson, working together with scientists from Merck Research Laboratories, to further evaluate tumor pathobiology and clinical outcomes to better pinpoint the tumor types most susceptible to the variety of drugs for different pathologies.

Dana-Farber established the CACS, which is supported by the Robert A. and Renee E. Belfer Foundation, in 2004. CACS is part of the Robert A. and Renee E. Belfer Institute for Innovative Cancer Science, which also houses the Arthur and Rochelle Belfer Center for Cancer Genomics.

"Collaborations with external partners are an integral and essential part of our oncology research and development strategy," says Stephen Friend M.D., Ph.D, senior vice president and franchise head, oncology, Merck Research Laboratories.
"Through this collaboration with Dana-Farber, one of the world's premier cancer centers, we hope to establish an open and collaborative relationship through our common goal of advancing cancer treatment," he says.

Aside from undisclosed upfront, milestone and R&D payments, the CACS-Merck collaboration could prove to be mutually beneficial.

"We are in the business of discovery and our efforts are at the preclinical phase and helping think about the translation of data," adds DePinho. "[Merck's] strength is in marketing and drug development. That's what makes this an attractive partnership. Our cultures mesh well."

 


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